Procalcitonin and lung ultrasound algorithm to diagnose severe pneumonia in critical paediatric patients (PROLUSP study). A randomised clinical trial

Lung ultrasound (LUS) in combination with a biomarker has not yet been studied. We propose a clinical trial where the primary aims are: 1. To assess whether an algorithm with LUS and procalcitonin (PCT) may be useful for diagnosing bacterial pneumonia; 2. To analyse the sensitivity and specificity of LUS vs chest X-ray (CXR). A 3-year clinical trial. Inclusion criteria: children younger than 18 years old with suspected pneumonia in a Paediatric Intensive Care Unit. Patients will be randomised into two groups: Experimental Group: LUS will be performed as first lung image. Control Group: CXR will be performed as first pulmonary image. Patients will be classified according to the image and the PCT: a) PCT 1 ng/mL, antibiotic therapy is recommended. This algorithm will help us to diagnose bacterial pneumonia and to prescribe the correct antibiotic treatment. A reduction of antibiotics per patient, of the treatment length, and of the exposure to ionizing radiation and in costs is expected

A training plan to implement lung ultrasound for diagnosing pneumonia in children

Lung ultrasound (LUS) for critical patients requires trained operators to perform them, though little information exists on the level of training required for independent practice. The aims were to implement a training plan for diagnosing pneumonia using LUS and to analyze the inter-observer agreement between senior radiologists (SRs) and pediatric intensive care physicians (PICPs). Prospective longitudinal and interventional study conducted in the Pediatric Intensive Care Unit of a tertiary hospital. Following a theoretical and practical training plan regarding diagnosing pneumonia using LUS, the concordance between SRs and the PICPs on their LUS reports was analyzed. Nine PICPs were trained and tested on both theoretical and practical LUS knowledge. The mean exam mark was 13.5/15. To evaluate inter-observer agreement, a total of 483 LUS were performed. For interstitial syndrome, the global Kappa coefficient (K) was 0.51 (95% CI 0.43-0.58). Regarding the presence of consolidation, K was 0.67 (95% CI 0.53-0.78), and for the consolidation pattern, K was 0.82 (95% CI 0.79-0.85), showing almost perfect agreement. Our training plan allowed PICPs to independently perform LUS and might improve pneumonia diagnosis. We found a high inter-observer agreement between PICPs and SRs in detecting the presence and type of consolidation on LUS

Thyroid hormones inhibit TGF-β signaling and attenuate fibrotic responses

TGF-β, the most potent profibrogenic factor, acts by activating SMAD (mothers against decapentaplegic) transcription factors, which bind to SMAD-binding elements in target genes. Here, we show that the thyroid hormone triiodothyronine (T3), through binding to its nuclear receptors (TRs), is able to antagonize transcriptional activation by TGF-β/SMAD. This antagonism involves reduced phosphorylation of SMADs and a direct interaction of the receptors with SMAD3 and SMAD4 that is independent of T3-mediated transcriptional activity but requires residues in the receptor DNA binding domain. T3 reduces occupancy of SMADbinding elements in response to TGF-β, reducing histone acetylation and inhibiting transcription. In agreement with this transcriptional cross-talk, T3 is able to antagonize fibrotic processes in vivo. Liver fibrosis induced by carbon tetrachloride is attenuated by thyroid hormone administration to mice, whereas aged TR knockout mice spontaneously accumulate collagen. Furthermore, skin fibrosis induced by bleomycin administration is also reduced by the thyroid hormones. These findings define an important function of the thyroid hormone receptors and suggest TR ligands could have beneficial effects to block the progression of fibrotic diseases.This work was supported by Grants BFU2011-28058 and BFU2014-53610P from Ministerio de Economía y Competitividad; S2011/BMD-2328 TIRONET from the Comunidad de Madrid; and RD12/0036/0030 from the Instituto de Salud Carlos III. The cost of this publication has been paid in part by FEDER fund

Avances en la resolución conjunta de los procesos costeros y portuarios para la predicción de la agitación en la bahía de Algeciras

Se agradece a la APBA la financiación dentro del proyecto “Algeciras Safeport”

Neuroprotection with Hypothermia and Allopurinol in an animal model of hypoxic-ischemic injury: Is it a gender question?

Abstract Background Hypoxic-ischemic encephalopathy (HIE) is one of the most important causes of neonatal brain injury. Therapeutic hypothermia (TH) is the standard treatment for term newborns after perinatal hypoxic ischemic injury (HI). Despite this, TH does not provide complete neuroprotection. Allopurinol seems to be a good neuroprotector in several animal studies, but it has never been tested in combination with hypothermia. Clinical findings show that male infants with (HI) fare more poorly than matched females in cognitive outcomes. However, there are few studies about neuroprotection taking gender into account in the results. The aim of the present study was to evaluate the potential additive neuroprotective effect of allopurinol when administrated in association with TH in a rodent model of moderate HI. Gender differences in neuroprotection were also evaluated Methods P10 male and female rat pups were subjected to HI (Vannucci model) and randomized into five groups: sham intervention (Control), no treatment (HI), hypothermia (HIH), allopurinol (HIA), and dual therapy (hypothermia and allopurinol) (HIHA). To evaluate a treatment's neuroprotective efficiency, 24 hours after the HI event caspase3 activation was measured. Damaged area and hippocampal volume were also measured 72 hours after the HI event. Negative geotaxis test was performed to evaluate early neurobehavioral reflexes. Learning and spatial memory were assessed via Morris Water Maze (MWM) test at 25 days of life. Results Damaged area and hippocampal volume were different among treatment groups (p = 0.001). The largest tissue lesion was observed in the HI group, followed by HIA. There were no differences between control, HIH, and HIHA. When learning process was analyzed, no differences were found. Females from the HIA group had similar results to the HIH and HIHA groups. Cleaved caspase 3 expression was increased in both HI and HIA. Despite this, in females cleaved caspase-3 was only differently increased in the HI group. All treated animals present an improvement in short-term (Negative geotaxis) and long-term (WMT) functional tests. Despite this, treated females present better long-term outcome. In short-term outcome no sex differences were observed. Conclusions Our results suggest that dual therapy confers great neuroprotection after an HI event. There were functional, histological, and molecular improvements in all treated groups. These differences were more important in females than in males. No statistically significant differences were found between HIHA and HIH; both of them present a great improvement. Our results support the idea of different regulation mechanisms and pathways of cell death, depending on gender

Major Adverse Cardiovascular Events in Coronary Type 2 Diabetic Patients: Identification of Associated Factors Using Electronic Health Records and Natural Language Processing

Patients with Type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) are at high risk of developing major adverse cardiovascular events (MACE). This is a multicenter, retrospective, and observational study performed in Spain aimed to characterize these patients in a real-world setting. Unstructured data from the Electronic Health Records were extracted by EHRead (R), a technology based on Natural Language Processing and machine learning. The association between new MACE and the variables of interest were investigated by univariable and multivariable analyses. From a source population of 2,184,662 patients, we identified 4072 adults diagnosed with T2DM and CAD (62.2% male, mean age 70 +/- 11). The main comorbidities observed included arterial hypertension, hyperlipidemia, and obesity, with metformin and statins being the treatments most frequently prescribed. MACE development was associated with multivessel (Hazard Ratio (HR) = 2.49) and single coronary vessel disease (HR = 1.71), transient ischemic attack (HR = 2.01), heart failure (HR = 1.32), insulin treatment (HR = 1.40), and percutaneous coronary intervention (PCI) (HR = 2.27), whilst statins (HR = 0.73) were associated with a lower risk of MACE occurrence. In conclusion, we found six risk factors associated with the development of MACE which were related with cardiovascular diseases and T2DM severity, and treatment with statins was identified as a protective factor for new MACE in this study

Impact of Advanced Age on the Incidence of Major Adverse Cardiovascular Events in Patients with Type 2 Diabetes Mellitus and Stable Coronary Artery Disease in a Real-World Setting in Spain

Patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) without myocardial infarction (MI) or stroke are at high risk for major cardiovascular events (MACEs). We aimed to provide real-world data on age-related clinical characteristics, treatment management, and incidence of major cardiovascular outcomes in T2DM-CAD patients in Spain from 2014 to 2018. We used EHRead (R) technology, which is based on natural language processing and machine learning, to extract unstructured clinical information from electronic health records (EHRs) from 12 hospitals. Of the 4072 included patients, 30.9% were younger than 65 years (66.3% male), 34.2% were aged 65-75 years (66.4% male), and 34.8% were older than 75 years (54.3% male). These older patients were more likely to have hypertension (OR 2.85), angina (OR 1.64), heart valve disease (OR 2.13), or peripheral vascular disease (OR 2.38) than those aged <65 years (p < 0.001 for all comparisons). In general, they were also more likely to receive pharmacological and interventional treatments. Moreover, these patients had a significantly higher risk of MACEs (HR 1.29; p = 0.003) and ischemic stroke (HR 2.39; p < 0.001). In summary, patients with T2DM-CAD in routine clinical practice tend to be older, have more comorbidities, are more heavily treated, and have a higher risk of developing MACE than is commonly assumed from clinical trial data

The MEDESS-GIB database: Tracking the Atlantic water inflow

On 9 September 2014, an intensive drifter deployment was carried out in the Strait of Gibraltar. In the frame of the MEDESS-4MS Project (EU MED Program), the MEDESS-GIB experiment consisted of the deployment of 35 satellite tracked drifters, mostly of CODE-type, equipped with temperature sensor sampling at a rate of 30min. Drifters were distributed along and on both sides of the Strait of Gibraltar. The MEDESS-GIB deployment plan was designed as to ensure quasi-synoptic spatial coverage. To this end, four boats covering an area of about 680NM2 in 6h were coordinated. As far as these authors know, this experiment is the most important exercise in the area in terms of number of drifters released. Collected satellite-tracked data along drifter trajectories have been quality controlled and processed to build the presented MEDESS-GIB database. This paper reports the MEDESS-GIB data set that comprises drifter trajectories, derived surface currents and in situ SST measurements collected along the buoys tracks. This series of data is available through the PANGAEA (Data Publisher for Earth and Environmental Science) repository, with the following doi:10.1594/PANGAEA.853701. Likewise, the MEDESS-GIB data will be incorporated as part of the Copernicus Marine historical products. The MEDESS-GIB data set provides a complete Lagrangian view of the surface inflow of Atlantic waters through the Strait of Gibraltar and thus, very useful data for further studies on the surface circulation patterns in the Alboran Sea, and their links with one of the most energetic Mediterranean Sea flows: the Algerian Current

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics